Nervous system function is commonly assessed by recording evoked potentials (EPs) in response to some stimulus. The EP is a voltage that reflects some combination of the electrical activity of large number of neurones that contribute to the response by being sufficiently close to the recording electrodes. The stimulus is often presented several times and the average response to the stimulus is computed. More recently alternative monitoring means for recording stimulus evoked responses (SERs) have come into practice, including changes in magnetic fields or optical signals generated by neural activity. Another response generated by the nervous system providing possible utility is the pupillary response. Similarly the electro-oculogram, or eye movements measured in other ways, could be used to derive a SER. Functional magnetic imaging can also quantify brain responses to produce an SER. Effects of the scattering, refraction or absorption of infrared radiation or T-rays reflecting neural activity might also be useful in producing SERs. The relatively non-invasive measurement provided by these recording means is desirable in the clinical setting. Evoked electrical potentials reflecting brain activity are easily recorded from electrodes placed upon the scalp. Magnetic, and infrared signals related to neural activity can be similarly recorded through the skin. In the case of monitoring means involving electromagnetic radiation such as infrared or T-rays it may be necessary to project these optical signals into the nervous system and then observe the effects of absorption, refraction or scattering or some collection of these parameters. A potential drawback of surface measurements, or eye movements, or the pupillary response is that, however they are measured, these evoked responses typically represent the collective activity of many neurones in response to the stimulus.
Monitoring means such as the relatively slow infrared method of Takahashi K., Ogata S., Atsumi Y., Yamamoto R., Shiotsuka S., Maki A., Yamashita Y., Yamamoto T., Koizumi H., Hirasawa H., and Igawa M., entitled “Activation of the visual cortex imaged by 24-channel near-infrared spectroscopy”, published in Journal of Biomedical Optics, volume 5, pages 93-96, would be useful. Monitoring means involving infrared signals that are biased towards measuring the rapid signals of the type described by: WOLF, M., WOLF, U., CHOI, J. H., GUPTA, R., SAFONOVA, L. P., PAUNESCU, L. A., MICHALOS, A. & GRATTON, E. (2002), entitled “Functional frequency-domain near-infrared spectroscopy detects fast neuronal signal in the motor cortex”, published in Neuroimage, volume 17, pages 1868-1875, are preferred as they provide high temporal resolution of neural activity.
Diseases affecting the nervous system may differentially impair component parts of the nervous system. For example separate parts of the retina are differentially affected by the common eye disease glaucoma. These changes to the retina result in localised decreases in visual performance in particular parts of the visual field. Another common neurological disease, multiple sclerosis, causes damage to small regions along myelinated nerves and neural pathways within the brain. Thus, in such cases it would be useful to test neural function with multiple stimuli concurrently in time, each stimulus testing a different component part of the nervous system, with or without some overlap in the stimulated domains, in what might be called Multi-stimulus Evoked Responses (MSERs). The ability to record responses to concurrently presented stimuli to different component parts of the nervous system would clearly reduce some of the problems inherent in classic methods for recording evoked responses, in that the responses would represent the activity of component parts of the nervous system rather than the massed response of some or all the stimulated parts. In the case of testing the visual field, a MSER would allow stimuli to be concurrently presented to multiple parts of the visual field. This would in principle allow more time-efficient mapping of the visual field. As few as one recording sensor placed on or near the eye or scalp could be used, thus making the time required to set up the monitoring means quite short. Thus, the problems of recording evoked responses in the clinic are reduced when responses to stimuli to multiple parts of the nervous system can be recorded by relatively few sensors. Of course this does not preclude the use of many sensors, the possibility of relatively few sensors is simply noted as a possibly useful feature of MSERs.
While some MSER methods have been proposed, the emphasis in the design of the stimulus sequences used to date has most often been to reduce the computational load when estimating the responses, largely by reducing the degree of correlation between the concurrently presented stimulus sequences. For example, Wiener, N (“Nonlinear problems in random theory”, New York, Wiley, 1958) proposed the use of continuous Gaussian distributed white noise sequences that in principle could be applied at the temporal modulation functions of the multiple stimuli presented for measurement of MSERs. Sutter, E (U.S. Pat. No. 4,846,567) proposed the use of special stimulus sequences called m-sequences where the stimulus sequence fluctuates between one of two levels in a strictly defined way. These two level m-sequences are a subset of a class of sequences that are said to be binary. These binary sequences vary between two about equally likely stimulus conditions and thus, unlike the stimuli proposed hereafter, never contain a null condition and are not sparse in the sense presented herein. Neither of the stimuli of Wiener or Sutter is designed to optimise responses from any particular part of the nervous system. Stimuli that permit the measurement of MSERs but which are optimised for assessing clinically relevant signals from the nervous system would be potentially more useful.
Of particular interest in assessment of neural function may be those parts of the nervous system that dynamically adapt to prevailing stimulus conditions by using what we will call response-regulating mechanisms. These neural systems are interesting from the point of view of studying neural performance because these response-regulating systems are often complex and strictly controlled. Thus, neural dysfunction might be readily observed in neural systems exhibiting strong response-regulating mechanisms. At the same time appropriate design of stimulus sequences might permit neural systems with response-regulating systems to produce larger and or more reliable responses. An example of response regulation of particular relevance to measuring the visual field by MSER methods is so called lateral masking, which occurs when many stimuli are present in the visual field at the same time. When the stimuli are near to each other the sensitivity to each of the stimuli is reduced, particularly in peripheral vision. In some neurological disorders like amblyopia or reading dyslexia lateral masking appears to operate in an abnormal way, so aside from undoing the potentially deleterious effects of lateral masking it is desirable to construct MSER stimuli that might enhance features of lateral masking for the purposes of studying it directly as a means of characterising diseases specifically effecting lateral masking.